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Human Adult White Matter Progenitor Cells Are Multipotent Neuroprogenitors Similar to Adult Hippocampal Progenitors

Lojewski, Xenia and Hermann, Andreas and Wegner, Florian and Araúzo-Bravo, Marcos J. and Hallmeyer-Elgner, Susanne and Kirsch, Matthias and Schwarz, Johannes and Schöler, Hans R. and Storch, Alexander (2014) Human Adult White Matter Progenitor Cells Are Multipotent Neuroprogenitors Similar to Adult Hippocampal Progenitors. Stem Cells Translational Medicine, 3 (4). pp. 458-469. ISSN 2157-6564. PMCID PMC3973711. http://resolver.caltech.edu/CaltechAUTHORS:20140825-134223184

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Abstract

Adult neural progenitor cells (aNPC) are a potential autologous cell source for cell replacement in neurologic diseases or for cell-based gene therapy of neurometabolic diseases. Easy accessibility, long-term expandability, and detailed characterization of neural progenitor cell (NPC) properties are important requisites for their future translational/clinical applications. aNPC can be isolated from different regions of the adult human brain, including the accessible subcortical white matter (aNPC_WM), but systematic studies comparing long-term expanded aNPC_WM with aNPC from neurogenic brain regions are not available. Freshly isolated cells from subcortical white matter and hippocampus expressed oligodendrocyte progenitor cell markers such as A2B5, neuron-glial antigen 2 (NG2), and oligodendrocyte transcription factor 2 (OLIG2) in ∼20% of cells but no neural stem cell (NSC) markers such as CD133 (Prominin1), Nestin, SOX2, or PAX6. The epidermal growth factor receptor protein was expressed in 18% of aNPC_WM and 7% of hippocampal aNPC (aNPC_HIP), but only a small fraction of cells, 1 of 694 cells from white matter and 1 of 1,331 hippocampal cells, was able to generate neurospheres. Studies comparing subcortical aNPCWM with their hippocampal counterparts showed that both NPC types expressed mainly markers of glial origin such as NG2, A2B5, and OLIG2, and the NSC/NPC marker Nestin, but no pericyte markers. Both NPC types were able to produce neurons, astrocytes, and oligodendrocytes in amounts comparable to fetal NSC. Whole transcriptome analyses confirmed the strong similarity of aNPC_WM to aNPC_HIP. Our data show that aNPCWM are multipotent NPC with long-term expandability similar to NPC from hippocampus, making them a more easily accessible source for possible autologous NPC-based treatment strategies.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.5966/sctm.2013-0117DOIArticle
http://stemcellstm.alphamedpress.org/content/3/4/458PublisherArticle
Additional Information:© 2014 AlphaMed Press. Received June 24, 2013; accepted for publication December 5, 2013; first published online in SCT M EXPRESS February 20, 2014. We thank Sylvia Kanzler for excellent technical assistance. We thank Sumi Srimasorn for mesenchymal stem cell marker stainings. This work was supported by the Bundesministerium für Bildung und Forschung (research program Gewinnung pluri- bzw. multipotenter Stammzellen, AZ: 01GN1006) to A.S., A.H., and H.R.S. X.L.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; A.H.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, financial support, final approval of manuscript; F.W., M.J.A.-B., S.H.-E., M.K., and J.S.: collection and assembly of data, data analysis and int erpretation, manuscript writing; H.R.S.: provision of study material, manuscript writing, financial support, administrative support; A.S.: conception and design, data analysis and interpretation, manuscript writing, financial support, administrative support.
Funders:
Funding AgencyGrant Number
Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany)AZ: 01GN1006
Subject Keywords:Neural progenitor cells; White matter; Hippocampus; Human adult brain; Fetal neural stem cells
PubMed Central ID:PMC3973711
Record Number:CaltechAUTHORS:20140825-134223184
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140825-134223184
Official Citation:Lojewski, X., Hermann, A., Wegner, F., Araúzo-Bravo, M. J., Hallmeyer-Elgner, S., Kirsch, M., . . . Storch, A. (2014). Human Adult White Matter Progenitor Cells Are Multipotent Neuroprogenitors Similar to Adult Hippocampal Progenitors. Stem Cells Translational Medicine, 3(4), 458-469. doi: 10.5966/sctm.2013-0117
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:48855
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:25 Aug 2014 23:19
Last Modified:25 Aug 2014 23:19

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